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Like nucleoside analogues, this class of drugs works against the reverse transcriptase enzyme. Non-nukes interfere directly with the action of the reverse transcriptase enzyme, preventing it from working properly. It is not yet clear where non-nukes fit in the overall picture of anti-HIV treatment. Studies are still underway to find out how best to use these drugs.

HIV becomes resistant to non-nukes very quickly. For this reason, non-nukes must be used in combination with at least two other drugs.

Most side effects of non-nukes (such as nausea, diarrhoea and headache) are generally fairly mild, but some can be severe and potentially dangerous. Rash is probably the most common side effect.

Anyone who develops a rash while using a non-nuke should consult their doctor as soon as possible. If the rash is accompanied by fever, skin blisters, itching or burning eyes, swelling, muscle or joint pain, or general malaise, the drug must be stopped.